Soumen Basak

In a multidisciplinary research program, we aim to characterize regulatory circuitries that enable crosstalk between various immune activating and homeostatic cues using systems biology tools.In sum, we are interested in understanding physiological and patho-physiological consequences of such cross-regulations in the context of

Mammalian cells receive and process signals from a variety of extra-cellular stimuli those engage “dedicated” signaling pathways to elicit appropriate cellular responses. In physiological settings, however, a variety of different stimuli are often impinged upon a single cell simultaneously activating multiple signaling pathways; thereby generatingthe possibility for crosstalk between these apparently insulated cell-signaling pathways. Our research interest lies in exploring the interplay between these “dedicated” signaling pathways and understanding the implications of such interdependent regulations in physiology and patho-physiology.

In particular, the NF-kappaB signaling system has the remarkable capacity to process signals from a variety of extracellular as well as intracellular cues, those include pathogen derived substances, host-derived cytokines, cell-differentiating and developmental cues, reactive oxygen species or metabolic substances. The NF-kappaB system receives signals through either the canonical or the non-canonical arms to potentially activate a dozen of transcription factors. In our laboratory, we have considered the pleiotropic NF-kB systemas a potential playerin mediating signaling crosstalk in varied physiological context. In a multidisciplinary research program that combines biochemistry, molecular biology, cell biology, mouse genetics and mathematical modeling, we aim to identify and characterize the crossregulatory elements embedded within the NF-kB system that enable crosstalk between immune activating and homeostatic cues. By simulating a computational model, we are generating conceptual framework in silicoon plausible crosstalk regulations. Using biochemical assays, such as Immunoblot analysis, EMSA, Real Time PCR etc., and genetic tools, including a panel of knockout cells,we are testing signaling crosstalk ex vivo. Finally, we are examining potential physiological or pathophysiological ramification of pathway crosstalks in vivo in murine model. One long-term objective of our research program is to eventually define connectivities between the NF-kB system and other important immune pathways, such as type-1 IFN system.

Our systems based approach not only promises new mechanistic insights into the dynamic control of immune responses but also has therapeutic importance. Targeting the proposed crosstalk components in inflammatory diseases and in pathogenesis bears the promise to reduce the devastating side effects that are often associated with the treatment regimes that target signaling hub molecules.